Many patients suffering from acute renal failure are treated with various forms of hemofiltration, known generally as Continuous Renal Replacement Therapy (CRRT). In hemofiltration, a patient's blood is routed into an extracorporeal circuit and led under pressure through a blood filter, or hemofilter. The hemofilter contains a semi-permeable membrane that separates water and waste solutes from the main flow of blood. The filtered blood is then returned to the patient. Hemodialysis, as another form of renal replacement therapy, differs from hemofiltration in that a dialysate fluid is made to flow along a side of the semi-permeable membrane opposite to the side where blood flows. Concentration gradients across the membrane encourage the migration of unwanted solutes out of the blood into the dialysate by osmosis. Hemodialysis usually can only be applied for a few hours per day, and as such, is more restrictive and sometimes less effective than pure hemofiltration. However, hemodialysis can be combined with hemofiltration to provide more complex blood filtration therapies.
Typically, a hemofilter or artificial kidney is used during CRRT therapy. The artificial kidney may be formed of hollow-fibers or closely separated plates, and is connected to a patient's bloodstream through an extracorporeal circuit. The supply from and the return to the blood of the patient can be made via two venous accesses, using a blood pump to provide the driving force for the transport of blood from the patient into the artificial kidney and back to the patient. An access providing the supply of blood to the artificial kidney can alternatively be made through an artery, and the return of the blood to the patient can be made through a vein. In this case, the arterial blood pressure provides the driving force to transport the blood, and blood pumps are not necessarily mandatory. However, a pump provides better control of blood flow, and renal replacement therapies using blood pumps are preferred.
Mimicking the natural filtering function of a kidney over a semipermeable membrane leads to a considerable loss of fluid from the blood, which is removed as the filtrate in the artificial kidney. Every liter of filtrate fluid removed in the artificial kidney contains a large fraction of the molecules that are dissolved in the plasma. The fraction of molecules that pass the semipermeable membrane depends on the chemical characteristics of the molecules, the structure of the membrane, and the transmembrane pressure (TMP). In order to keep the blood volume of the patient constant, a substitution fluid is usually added in approximately the same amount to the bloodstream in the extracorporeal circuit. The substitution fluid commonly used is conventional infusion fluid comprising a physiological saline solution.
Performing CRRT usually requires the use of a CRRT machine for controlling blood flow through the extracorporeal circuit. Typically, a CRRT machine draws blood from a patient through an access line using a blood pump (e.g., a peristaltic pump), and returns the blood to the patient through a return line. The flow rate of the blood pump, the design of the artificial kidney, and the type of CRRT therapy used determine the fluid loss rate from the bloodstream through the filter.
Pressure sensors throughout the extracorporeal circuit may be used to sense and alarm fluid flow at various points. For example, an access line pressure sensor may sense pressure of blood entering the extracorporeal circuit, and generate an alarm in the event the sensor senses an out-of-range condition. Similarly, a return line pressure sensor may also sense and transmit pressure signals and generate alarms.
Pressure sensors placed before the hemofilter, in the filtrate outflow, and in the return line provide measurements needed to calculate TMP or the pressure drop (PD) in blood flowing through the artificial kidney.
During therapy, dialysate fluid flows into the dialysate compartment of the artificial kidney, and a filtration pump is used to remove used dialysate (or effluent) from the blood circulating through the artificial kidney. The effluent is collected inside a filtration container and may also be weighed to monitor fluid loss.
A procedural safeguard may be provided where plasma fluid lost through the artificial kidney can be compared to the amount of substitution fluid added to the extracorporeal circuit. The difference yielded by this comparison is the total fluid loss (or gain) TFL. In most therapies, TFL is ideally maintained at zero, i.e., no net loss of vital fluids.
A common technique for detecting TFL in CRRT machines: direct regulation and differential regulation. Direct regulation calculates TFL by reading weight values for both filtration fluid and substitution fluid at regular time intervals. The weighed value of filtration fluid is compared to an expected value of filtration fluid calculated by the CRRT machine. Any difference between weighed and expected values yields a correction signal that adjusts filtration flow rate caused by the filtration pump. Similarly, the weighed value of substitution fluid is compared to an expected value of substitution fluid calculated by the CRRT machine. Any difference between weighed and expected values yields a correction signal that adjusts substitution flow rate caused by the substitution pump. In this manner, the performance of each pump is individually controlled to meet predetermined performance criteria. Differential regulation calculates TFL by continuously measuring weight change of filtration and substitution fluids over the same time period. The change in filtration fluid in a single period is subtracted from the change in substitution fluid over the same time period, yielding a value for TFL. This value is compared to a predetermined value of expected TFL. If the comparison yields a difference, a correction signal is generated to balance the system, i.e., to govern one or both of the filtration and substitution pump flow rates and cause TFL to converge toward zero or some other desired value.
Both direct and differential regulation schemes have limitations. When regulation cannot achieve a desired balance, an alarm may be generated. In state-of-the-art net fluid removal (NFR) control systems, upon error compensation, NFR rate changes are not continuously, i.e. both short-term and within long periods over e.g. several hours, limited to a low level which is not harmful for the patient.